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1.
Brain Imaging Behav ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35552993

RESUMO

This study examined how resting-state functional magnetic resonance imaging (rs-fMRI) data quality and availability relate to clinical and sociodemographic variables within the Adolescent Brain Cognitive Development Study. A sample of participants with an adequate sample of quality baseline rs-fMRI data containing low average motion (framewise displacement ≤ 0.15; low-noise; n = 4,356) was compared to a sample of participants without an adequate sample of quality data and/or containing high average motion (higher-noise; n = 7,437) using Chi-squared analyses and t-tests. A linear mixed model examined relationships between clinical and sociodemographic characteristics and average head motion in the sample with low-noise data. Relative to the sample with higher-noise data, the low-noise sample included more females, youth identified by parents as non-Hispanic white, and youth with married parents, higher parent education, and greater household incomes (ORs = 1.32-1.42). Youth in the low-noise sample were also older and had higher neurocognitive skills, lower BMIs, and fewer externalizing and neurodevelopmental problems (ds = 0.12-0.30). Within the low-noise sample, several clinical and demographic characteristics related to motion. Thus, participants with low-noise rs-fMRI data may be less representative of the general population and motion may remain a confound in this sample. Future rs-fMRI studies of youth should consider these limitations in the design and analysis stages in order to optimize the representativeness and clinical relevance of analyses and results.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35488084

RESUMO

Lenrispodun is a potent and highly selective inhibitor of phosphodiesterase (PDE) type 1, which is thought to prolong intracellular second messenger signaling within cortical and subcortical dopaminergic brain regions. This is the first study of a PDE1 inhibitor in healthy volunteers using behavioral and neuroimaging approaches to examine its effects on neural targets and to provide a safety and tolerability assessment. The primary objectives were to determine whether lenrispodun induces changes in BOLD fMRI signals in the inferior frontal gyrus (IFG) during the stop signal task, and the dorsal anterior insula (dAI) during the extinction phase of a fear conditioning/extinction task. Using a double-blind, placebo-controlled, within-subjects design, 26 healthy individuals (22 completed all fMRI sessions) received in random order a single oral dose of placebo, lenrispodun 1.0 milligram (mg) or lenrispodun 10.0 mg and completed several tasks in the scanner including the stop signal (n = 24) and fear conditioning/extinction tasks (n = 22). Prespecified region-of-interest analyses for the IFG and dAI were computed using linear mixed models. Lenrispodun induced increases in IFG activity during the stop signal task at 1.0 mg (Cohen's d = 0.63) but not 10.0 mg (Cohen's d = 0.07) vs. placebo. Lenrispodun did not induce changes in dAI activity during fear extinction at either dose. Exploratory outcomes revealed changes in cardiac interoception. Lenrispodun administration was well-tolerated. These results provide evidence that 1.0 mg lenrispodun selectively improved neural inhibitory control without altering fear extinction processing. Future investigations should determine whether lenrispodun improves inhibitory control in target populations such as individuals with attention deficit hyperactivity disorder. Trial registration: ClinicalTrials.gov identifier: NCT03489772.

3.
Front Neurosci ; 16: 834827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360171

RESUMO

Real-time fMRI (rtfMRI) has enormous potential for both mechanistic brain imaging studies or treatment-oriented neuromodulation. However, the adaption of rtfMRI has been limited due to technical difficulties in implementing an efficient computational framework. Here, we introduce a python library for real-time fMRI (rtfMRI) data processing systems, Real-Time Processing System in python (RTPSpy), to provide building blocks for a custom rtfMRI application with extensive and advanced functionalities. RTPSpy is a library package including (1) a fast, comprehensive, and flexible online fMRI image processing modules comparable to offline denoising, (2) utilities for fast and accurate anatomical image processing to define an anatomical target region, (3) a simulation system of online fMRI processing to optimize a pipeline and target signal calculation, (4) simple interface to an external application for feedback presentation, and (5) a boilerplate graphical user interface (GUI) integrating operations with RTPSpy library. The fast and accurate anatomical image processing utility wraps external tools, including FastSurfer, ANTs, and AFNI, to make tissue segmentation and region of interest masks. We confirmed that the quality of the output masks was comparable with FreeSurfer, and the anatomical image processing could complete in a few minutes. The modular nature of RTPSpy provides the ability to use it for a simulation analysis to optimize a processing pipeline and target signal calculation. We present a sample script for building a real-time processing pipeline and running a simulation using RTPSpy. The library also offers a simple signal exchange mechanism with an external application using a TCP/IP socket. While the main components of the RTPSpy are the library modules, we also provide a GUI class for easy access to the RTPSpy functions. The boilerplate GUI application provided with the package allows users to develop a customized rtfMRI application with minimum scripting labor. The limitations of the package as it relates to environment-specific implementations are discussed. These library components can be customized and can be used in parts. Taken together, RTPSpy is an efficient and adaptable option for developing rtfMRI applications. Code available at: https://github.com/mamisaki/RTPSpy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35292905

RESUMO

Mindfulness training (MT) promotes the development of one's ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens' d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).

5.
Brain Sci ; 12(3)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35326319

RESUMO

Mindfulness training (MT) reduces self-referential processing and promotes interoception, the perception of sensations from inside the body, by increasing one's awareness of and regulating responses to them. The posterior cingulate cortex (PCC) and the insular cortex (INS) are considered hubs for self-referential processing and interoception, respectively. Although MT has been consistently found to decrease PCC, little is known about how MT relates to INS activity. Understanding links between mindfulness and interoception may be particularly important for informing mental health in adolescence, when neuroplasticity and emergence of psychopathology are heightened. We examined INS activity during real-time functional magnetic resonance imaging neurofeedback-augmented mindfulness training (NAMT) targeting the PCC. Healthy adolescents (N = 37; 16 female) completed the NAMT task, including Focus-on-Breath (MT), Describe (self-referential processing), and Rest conditions, across three neurofeedback runs and two non-neurofeedback runs (Observe, Transfer). Regression coefficients estimated from the generalized linear model were extracted from three INS subregions: anterior (aINS), mid (mINS), and posterior (pINS). Mixed model analyses revealed the main effect of run for Focus-on-Breath vs. Describe contrast in aINS [R2 = 0.39] and pINS [R2 = 0.33], but not mINS [R2 = 0.34]. Post hoc analyses revealed greater aINS activity and reduced pINS activity during neurofeedback runs, and such activities were related to lower self-reported life satisfaction and less pain behavior, respectively. These findings revealed the specific involvement of insula subregions in rtfMRI-nf MT.

6.
Data Brief ; 42: 108014, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35310819

RESUMO

Neuroticism as a personality trait represents a heritable risk for psychiatric disorders. The polygenic risk score for neuroticism (N-PRS) is used to study genetic vulnerability to neuroticism. The current data present the association of the genetic risk for neuroticism to neural reward-punishment processing using functional magnetic resonance imaging. N-PRS was computed based on the individual's genotype information and a genome-wide association study on the UK Biobank data. While individuals performed a monetary incentive delay task, their neural activations for upcoming incentives (reward: gain, punishment: loss) were measured in blood oxygen level dependent (BOLD) signals during the delay phase. Multivariate ANCOVAs were used to analyze BOLD signals for finding the association between N-PRS and reward-punishment processing by the incentive valence (Related research article: H. Park, K.L. Forthman, R. Kuplicki, T.A. Victor, Tulsa 1000 Investigators, H.W. Yeh, W.K. Thompson, M.P. Paulus, Polygenic risk for neuroticism modulates response to gains and losses in the amygdala and caudate: evidence from a clinical cohort. J. Affect. Disord. 293 (2021) 124-132. https://doi.org/10.1016/j.jad.2021.06.016). These data can be used as reference data for future studies examining the role of the genetic propensity for personality traits in the context of psychiatric disorders.

7.
Nat Protoc ; 17(3): 567-595, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35121856

RESUMO

Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants' characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: 'Participants' Characteristics', 'General fMRI Information', 'General Task Information', 'Cue Information', 'Craving Assessment Inside Scanner', 'Craving Assessment Outside Scanner' and 'Pre- and Post-Scanning Considerations'. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the 'General fMRI Information' category were reported in 90.5% of the reviewed papers, items in the 'Pre- and Post-Scanning Considerations' category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.


Assuntos
Lista de Checagem , Imageamento por Ressonância Magnética , Sinais (Psicologia) , Técnica Delfos , Humanos , Reprodutibilidade dos Testes
8.
Biol Psychol ; 169: 108286, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35149138

RESUMO

Unmedicated individuals with major depressive disorder (MDD) show abnormal interoception, but it is unclear whether antidepressant treatment via serotonergic medication alters this relationship. The current cross-sectional study examined associations between neural and behavioral indices of interoceptive processing and chronic serotonergic medication administration in MDD. 47 selective serotonin reuptake inhibitor (SSRI)-medicated MDD (MDD-SSRI) individuals were propensity-matched with 48 unmedicated current MDD (MDD-UnMed) and 41 healthy comparison (HC) participants on demographics including age, sex, body mass index, education, as well as on dimensional scales of symptom severity including depression and anxiety. All participants completed an interoceptive attention task during functional magnetic resonance imaging, and a behavioral heartbeat tapping task under three conditions: Guessing, No Guessing, and Breath Hold. Relative to HC, both MDD groups: (1) exhibited lower mid-insula, amygdala, putamen, and caudate activation during interoceptive versus exteroceptive attention; and (2) showed poorer heartbeat tapping performance during the Breath Hold condition. However, the MDD-SSRI group reported higher intensity ratings of heartbeat and stomach sensations than MDD-UnMed and HC during the interoceptive attention task. These findings suggest that the attenuated patterns of neural activation observed in depressed individuals during interoceptive attention are not ameliorated by the chronic administration of serotonergic medications. However, amplified interoceptive sensation ratings suggest a potential impact of chronic serotonergic medication on conscious experiences of internal body states. Future investigations will need to determine the extent to which serotonergic medications acutely influence interoceptive processing, and whether such changes play a role in therapeutic responses during treatment initiation.


Assuntos
Transtorno Depressivo Maior , Interocepção , Atenção/fisiologia , Estudos Transversais , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Interocepção/fisiologia , Imageamento por Ressonância Magnética/métodos
9.
JAMA Psychiatry ; 79(4): 323-332, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35107563

RESUMO

IMPORTANCE: ß-Adrenergic stimulation elicits heart palpitations and dyspnea, key features of acute anxiety and sympathetic arousal, yet no neuroimaging studies have examined how the pharmacologic modulation of interoceptive signals is associated with fear-related neurocircuitry in individuals with generalized anxiety disorder (GAD). OBJECTIVE: To examine the neural circuitry underlying autonomic arousal induced via isoproterenol, a rapidly acting, peripheral ß-adrenergic agonist akin to adrenaline. DESIGN, SETTING, AND PARTICIPANTS: This crossover randomized clinical trial of 58 women with artifact-free data was conducted from January 1, 2017, to November 31, 2019, at the Laureate Institute for Brain Research in Tulsa, Oklahoma. EXPOSURES: Functional magnetic resonance imaging was used to assess neural responses during randomized intravenous bolus infusions of isoproterenol (0.5 and 2.0 µg) and saline, each administered twice in a double-blind fashion. MAIN OUTCOMES AND MEASURES: Blood oxygen level-dependent responses across the whole brain during isoproterenol administration in patients with GAD vs healthy comparators. Cardiac and respiratory responses, as well as interoceptive awareness and anxiety, were also measured during the infusion protocol. RESULTS: Of the 58 female study participants, 29 had GAD (mean [SD] age, 26.9 [6.8] years) and 29 were matched healthy comparators (mean [SD] age, 24.4 [5.0] years). During the 0.5-µg dose of isoproterenol, the GAD group exhibited higher heart rate responses (b = 5.34; 95% CI, 2.06-8.61; P = .002), higher intensity ratings of cardiorespiratory sensations (b = 8.38; 95% CI, 2.05-14.71; P = .01), higher levels of self-reported anxiety (b = 1.04; 95% CI, 0.33-1.76; P = .005), and significant hypoactivation in the ventromedial prefrontal cortex (vmPFC) that was evident throughout peak response (Cohen d = 1.55; P < .001) and early recovery (Cohen d = 1.52; P < .001) periods. Correlational analysis of physiological and subjective indexes and percentage of signal change extracted during the 0.5-µg dose revealed that vmPFC hypoactivation was inversely correlated with heart rate (r56 = -0.51, adjusted P = .001) and retrospective intensity of both heartbeat (r56 = -0.50, adjusted P = .002) and breathing (r56 = -0.44, adjusted P = .01) sensations. Ventromedial prefrontal cortex hypoactivation correlated inversely with continuous dial ratings at a trend level (r56 = -0.38, adjusted P = .051), whereas anxiety (r56 = -0.28, adjusted P = .27) and chronotropic dose 25 (r56 = -0.14, adjusted P = .72) showed no such association. CONCLUSIONS AND RELEVANCE: In this crossover randomized clinical trial, women with GAD exhibited autonomic hypersensitivity during low levels of adrenergic stimulation characterized by elevated heart rate, heightened interoceptive awareness, increased anxiety, and a blunted neural response localized to the vmPFC. These findings support the notion that autonomic hyperarousal may be associated with regulatory dysfunctions in the vmPFC, which could serve as a treatment target to help patients with GAD more appropriately appraise and regulate signals of sympathetic arousal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02615119.


Assuntos
Adrenérgicos , Transtornos de Ansiedade , Adulto , Transtornos de Ansiedade/tratamento farmacológico , Feminino , Humanos , Isoproterenol/farmacologia , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Estudos Retrospectivos , Adulto Jovem
10.
Sci Rep ; 12(1): 861, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039595

RESUMO

This double-blind, randomized, within-subjects design evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females, 10 males) underwent a functional magnetic resonance imaging scan while performing a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from serum and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. These findings are consistent with the hypothesis that miR-27b could be an important messaging molecule that is associated with regulating the processing of positive or negative valenced information.


Assuntos
Encéfalo/fisiologia , Voluntários Saudáveis/psicologia , Ibuprofeno/farmacologia , Processos Mentais/efeitos dos fármacos , Motivação/genética , Recompensa , Encéfalo/diagnóstico por imagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Ibuprofeno/administração & dosagem , Imageamento por Ressonância Magnética , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/fisiologia , Efeito Placebo
11.
Brain Stimul ; 15(2): 337-351, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35042056

RESUMO

BACKGROUND: Abnormalities in frontoparietal network (FPN) were observed in many neuropsychiatric diseases including substance use disorders. A growing number of studies are using dual-site-tACS with frontoparietal synchronization to engage this network. However, a computational pathway to inform and optimize parameter space for frontoparietal synchronization is still lacking. In this case study, in a group of participants with methamphetamine use disorders, we proposed a computational pathway to extract optimal electrode montage while accounting for stimulation intensity using structural and functional MRI. METHODS: Sixty methamphetamine users completed an fMRI drug cue-reactivity task. Four main steps were taken to define electrode montage and adjust stimulation intensity using 4x1 high-definition (HD) electrodes for a dual-site-tACS; (1) Frontal seed was defined based on the maximum electric fields (EF) predicted by simulation of HD montage over DLPFC (F3/F4 in EEG 10-10), (2) frontal seed-to-whole brain context-dependent correlation was calculated to determine connected regions to frontal seeds, (3) center of connected cluster in parietal cortex was selected as a location for placing the second set of HD electrodes to shape the informed montage, (4) individualized head models were used to determine optimal stimulation intensity considering underlying brain structure. The informed montage was compared to montages with large electrodes and classic frontoparietal HD montages (F3-P3/F4-P4) in terms of tACS-induced EF and ROI-to-ROI task-based/resting-state connectivity. RESULTS: Compared to the large electrodes, HD frontoparietal montages allow for a finer control of the spatial peak fields in the main nodes of the FPN at the cost of lower maximum EF (large-pad/HD: max EF[V/m] = 0.37/0.11, number of cortical sub-regions that EF exceeds 50% of the max = 77/13). For defining stimulation targets based on EF patterns, using group-level head models compared to a single standard head model results in comparable but significantly different seed locations (6.43 mm Euclidean distance between the locations of the frontal maximum EF in standard-space). As expected, significant task-based/resting-state connections were only found between frontal-parietal locations in the informed montage. Cue-induced craving score was correlated with frontoparietal connectivity only in the informed montage (r = -0.24). Stimulation intensity in the informed montage, and not in the classic HD montage, needs 40% reduction in the parietal site to reduce the disparity in EF between stimulation sites. CONCLUSION: This study provides some empirical insights to montage and dose selection in dual-site-tACS using individual brain structures and functions and proposes a computational pathway to use head models and functional MRI to define (1) optimum electrode montage for targeting FPN in a context of interest (drug-cue-reactivity) and (2) proper transcranial stimulation intensity.


Assuntos
Metanfetamina , Doenças do Sistema Nervoso , Estimulação Transcraniana por Corrente Contínua , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Lobo Parietal/diagnóstico por imagem , Estimulação Transcraniana por Corrente Contínua/métodos
12.
Depress Anxiety ; 39(1): 19-25, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34516701

RESUMO

BACKGROUND: The utility of brain-based biomarkers for psychiatric disorders hinges among other factors on their ability to explain a significant portion of the phenotypic variance. In particular, many small scale studies have been unable to arbitrate whether structural or functional magnetic resonance imaging has potential to be a biological marker for these disorders. METHODS: This study conducted a meta-analysis to examine the relationship between study power and published effect sizes for the relationship between affective symptoms and structural or functional magnetic resonance imaging measures. The current analyses are based on 821 brain-affective symptom association effect sizes derived from 120 publications, which employed a univariate region-of-interest approach. RESULTS: For self-assessed affective symptoms published brain imaging measures accounted for on average 8% (confidence interval: 1.6%-23%) of between-subject variation. This average effect size was based mostly on studies with small sample sizes, which have likely led to inflation of these effect size estimates. CONCLUSIONS: These findings support the conclusion that brain imaging measures currently account for a smaller proportion of the interindividual variance in affective symptoms than has been previously reported. The current findings support the need for both large-sample clinical studies and new statistical and theoretical models to more robustly capture systematic variance of brain-affective symptom relationships.


Assuntos
Sintomas Afetivos , Neuroimagem , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
13.
Viruses ; 13(12)2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34960745

RESUMO

INTRODUCTION: Interoception, defined as the sense of the internal state of one's body, helps motivate goal-directed behavior. Prior work has shown that methamphetamine (METH) use disorder is associated with altered interoception, and that this may contribute to risky behavior. As people with HIV (PWH) may also experience disrupted bodily sensations (e.g., neuropathy), an important question is whether PWH with a history of METH use disorder might exhibit greater impairment of interoceptive processing. METHODS: Eighty-three participants stratified by HIV infection and a past history of methamphetamine use disorder experienced a soft touch paradigm that included slow brush strokes on the left forearm and palm during blood-oxygen level-dependent functional MRI acquisition. To assess differences in interoception and reward, voxelwise analyses were constrained to the insula, a hub for the evaluation of interoceptive cues, and the striatum, which is engaged in reward processing. RESULTS: Overall, individuals with a history of METH use disorder had an attenuated neural response to pleasant touch in both the insula and striatum. Longer abstinence was associated with greater neural response to touch in the insula, suggesting some improvement in responsivity. However, only PWH with no METH use disorder history had lower brain activation in the insula relative to non-using seronegative controls. CONCLUSIONS: Our findings suggest that while METH use disorder history and HIV infection independently disrupt the neural processes associated with interoception, PWH with METH use disorder histories do not show significant differences relative to non-using seronegative controls. These findings suggest that the effects of HIV infection and past methamphetamine use might not be additive with respect to interoceptive processing impairment.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Corpo Estriado/fisiopatologia , Infecções por HIV/fisiopatologia , Interocepção , Tato , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Feminino , Infecções por HIV/psicologia , Humanos , Imageamento por Ressonância Magnética , Masculino
14.
BMC Psychiatry ; 21(1): 582, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798853

RESUMO

BACKGROUND: Adherence to treatment, i.e. the extent to which a patient's therapeutic engagement coincides with the prescribed treatment, is among the most important problems in mental health care. The current study investigated the influence of pairing an acute positive reinforcing dopaminergic/noradrenergic effect (methylphenidate, MPH) with a standard antidepressant on the rates of adherence to medication treatment. The primary objective of this study was to determine whether MPH + escitalopram resulted in higher rates of medication adherence relative to placebo + escitalopram. METHODS: Twenty participants with moderate to severe depression were 1-1 randomized to either (1) 5 mg MPH + 10 mg escitalopram or (2) placebo + 10 mg escitalopram with the possibility for a dose increase at 4 weeks. A Bayesian analysis was conducted to evaluate the outcomes. RESULTS: First, neither percent Pill count nor Medication Electronic Monitoring System adherence showed that MPH was superior to placebo. In fact, placebo showed slightly higher adherence rates on the primary (7.82% better than MPH) and secondary (7.07% better than MPH) outcomes. There was a less than 25% chance of MPH augmentation showing at least as good or better adherence than placebo. Second, both groups showed a significant effect of treatment on the QIDS-SR with a median effect of an 8.6-point score reduction. Third, neither subjective measures of adherence attitudes nor socio-demographic covariates had a significant influence on the primary or secondary outcome variables. CONCLUSIONS: These data do not support the use of MPH to increase adherence to antidepressant medication in individuals with moderate to severe depression. CLINICALTRIALS. GOV IDENTIFIER: NCT03388164 , registered on 01/02/2018.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Antidepressivos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Teorema de Bayes , Estimulantes do Sistema Nervoso Central/uso terapêutico , Método Duplo-Cego , Humanos , Metilfenidato/uso terapêutico , Projetos Piloto , Resultado do Tratamento
15.
J Affect Disord ; 295: 873-882, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706458

RESUMO

INTRODUCTION: Treatment effectiveness for major depressive disorder (MDD) is often affected by client non-adherence, dropout, and non-response. Identification of client characteristics predicting successful treatment completion and/or response (i.e., symptom reduction) may be an important tool to increase intervention effectiveness. It is unclear whether neural attenuations in reward processing associated with MDD predict behavioral treatment outcome. METHODS: This study aimed to determine whether blunted neural responses to reward at baseline differentiate MDD (n = 60; 41 with comorbid anxiety) and healthy control (HC; n = 40) groups; and predict MDD completion of and response to 7-10 sessions of behavior therapy. Participants completed a monetary incentive delay (MID) task. The N200, P300, contingent negative variation (CNV) event related potentials (ERPs) and behavioral responses (reaction time [RT], correct hits) were quantified and extracted for cross-sectional group analyses. ERPs and behavioral responses demonstrating group differences were then used to predict therapy completion and response within MDD. RESULTS: MDD exhibited faster RT and smaller P300 amplitudes than HC across conditions. Within the MDD group, treatment completers (n = 37) exhibited larger P300 amplitudes than non-completers (n = 21). LIMITATIONS: This study comprises secondary analyses of EEG data; thus task parameters are not optimized to examine feedback ERPs from the paradigm. We did not examine heterogenous presentations of MDD; however, severity and comorbidity did not influence findings. CONCLUSIONS: Previous studies suggest that P300 is an index of motivational salience and stimulus resource allocation. In sum, individuals who deploy greater neural resources to task demands are more likely to persevere in behavioral therapy.


Assuntos
Transtorno Depressivo Maior , Estudos Transversais , Transtorno Depressivo Maior/terapia , Humanos , Motivação , Tempo de Reação , Recompensa
16.
Brain Behav Immun Health ; 15: 100271, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34589776

RESUMO

BACKGROUND: Substance use disorder emerges from a complex interaction between genetic predisposition, life experiences, exposure, and subsequent adaptation of biological systems to the repeated use of drugs. Recently, investigators have proposed that the human microbiota may play a role in brain health and disease. In particular, the human oral microbiome is a distinct and diverse ecological niche with its composition influenced by external factors such as lifestyle, diet, and oral hygiene. This investigation examined whether individuals with substance use disorder (SU) show a different oral microbiome pattern and whether this pattern is sufficient to delineate the SU group from healthy comparison (HC) subjects. METHODS: Participants were a sub-sample (N â€‹= â€‹177) of the Tulsa 1000 (T-1000) project. We analyzed 123 SU and 54 HC subjects using 16S rRNA marker gene sequencing to characterize the oral microbiome. RESULTS: The groups differed significantly based on the UniFrac distance, a phylogenetic-based measure of beta diversity, but did not differ in alpha diversity. Using a machine learning approach, microbiome features combined with socio-demographic variables successfully categorized group membership with 87%-92% accuracy, even after controlling for external factors such as smoking or alcohol consumption. SU individuals with relatively lower diversity also reported higher levels of negative reinforcement experiences associated with their primary substance of abuse. CONCLUSIONS: Oral microbiome features are useful to sufficiently differentiate SU from HC subjects. There is some evidence that subjects whose drug use is driven by negative reinforcement show an impoverished oral microbiome. Taken together, the oral microbiome may help to understand the dysfunctional biological processes that promote substance use or may be pragmatically useful as a risk or severity biological marker.

17.
Transl Psychiatry ; 11(1): 464, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493708

RESUMO

Human cytomegalovirus (HCMV) is a neurotropic herpes virus known to cause neuropathology in patients with impaired immunity. Previously, we reported a reduction in the gray matter volume (GMV) of several brain regions in two independent samples of participants who were seropositive for HCMV (HCMV+) compared to matched participants who were seronegative for HCMV (HCMV-). In addition to an independent replication of the GMV findings, this study aimed to examine whether HCMV+ was associated with differences in resting-state functional connectivity (rsfMRI-FC). After balancing on 11 clinical/demographic variables using inverse probability of treatment weighting (IPTW), GMV and rsfMRI-FC were obtained from 99 participants with major depressive disorder (MDD) who were classified into 42 HCMV+ and 57 HCMV- individuals. Relative to the HCMV- group, the HCMV+ group showed a significant reduction of GMV in nine cortical regions. Volume reduction in the right lateral orbitofrontal cortex (standardized beta coefficient (SBC) = -0.32, [95%CI, -0.62 to -0.02]) and the left pars orbitalis (SBC = -0.34, [95%CI, -0.63 to -0.05]) in the HCMV+ group was also observed in the previous study. Regardless of the parcellation method or analytical approach, relative to the HCMV- group, the HCMV+ group showed hypoconnectivity between the hubs of the sensorimotor network (bilateral postcentral gyrus) and the hubs of the salience network (bilateral insula) with effect sizes ranging from SBC = -0.57 to -0.99. These findings support the hypothesis that a positive HCMV serostatus is associated with altered connectivity of regions that are important for stress and affective processing and further supports a possible etiological role of HCMV in depression.


Assuntos
Infecções por Citomegalovirus , Transtorno Depressivo Maior , Encéfalo , Infecções por Citomegalovirus/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
18.
PLoS One ; 16(9): e0252108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34525108

RESUMO

Normative modeling, a group of methods used to quantify an individual's deviation from some expected trajectory relative to observed variability around that trajectory, has been used to characterize subject heterogeneity. Gaussian Processes Regression includes an estimate of variable uncertainty across the input domain, which at face value makes it an attractive method to normalize the cohort heterogeneity where the deviation between predicted value and true observation is divided by the derived uncertainty directly from Gaussian Processes Regression. However, we show that the uncertainty directly from Gaussian Processes Regression is irrelevant to the cohort heterogeneity in general.


Assuntos
Estudos de Casos e Controles , Análise de Regressão , Humanos , Modelos Teóricos , Distribuição Normal , Incerteza
19.
Behav Ther ; 52(5): 1080-1092, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34452663

RESUMO

A developing area of research suggests that there may be a relationship between interoception and suicidal behavior. For example, it was recently reported that individuals who made a suicide attempt within the previous 5 years exhibit behavioral and neural abnormalities across multiple domains of interoception relative to nonattempters. This included increased tolerance for aversive sensations of pain and dyspnea, reduced heartbeat-perception accuracy, and blunted insula activity during attention to cardiac sensations. However, the degree to which interoceptive deficits persist following a suicidal attempt is unknown. In the current study, we examined differences between individuals with a remote history of suicide attempts (greater than 5 years ago; N = 56) versus those with no history of attempts (N = 240). We found that remote suicide attempters demonstrated greater pain tolerance and lower ratings of stress during a cold-pressor challenge and lower ratings of suffocation during a breath-hold challenge, as compared to nonattempters. In contrast, there were no group differences in breath-hold duration, interoceptive accuracy on a heartbeat-tapping task, or insula activation during cardiac attention. An exploratory resting-state functional connectivity analysis of individuals with suicide attempts in the past 5 years (N = 23), individuals with more remote histories of suicide attempts (N = 39), and nonattempters (N = 232) revealed preliminary and subtle evidence of differences in insula connectivity with areas of the temporal cortex in remote suicide attempters. Taken together, these findings suggest that blunted affective responses to aversive interoceptive sensations is an enduring characteristic of suicide attempters, even when assessed many years after a suicide attempt, whereas differences in the experience of nonaversive interoceptive sensations may be less persistent.


Assuntos
Interocepção , Ideação Suicida , Frequência Cardíaca , Humanos , Sensação , Tentativa de Suicídio
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